EP2451840A4 - Design of stable and aggregation free antibody fc molecules through ch3 domain interface engineering - Google Patents

Design of stable and aggregation free antibody fc molecules through ch3 domain interface engineering

Info

Publication number
EP2451840A4
EP2451840A4 EP10797631.8A EP10797631A EP2451840A4 EP 2451840 A4 EP2451840 A4 EP 2451840A4 EP 10797631 A EP10797631 A EP 10797631A EP 2451840 A4 EP2451840 A4 EP 2451840A4
Authority
EP
European Patent Office
Prior art keywords
molecules
stable
design
free antibody
domain interface
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP10797631.8A
Other languages
German (de)
French (fr)
Other versions
EP2451840B1 (en
EP2451840A1 (en
Inventor
Gunasekaran Kannan
Hongxing Zhou
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Amgen Inc
Original Assignee
Amgen Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Amgen Inc filed Critical Amgen Inc
Publication of EP2451840A1 publication Critical patent/EP2451840A1/en
Publication of EP2451840A4 publication Critical patent/EP2451840A4/en
Application granted granted Critical
Publication of EP2451840B1 publication Critical patent/EP2451840B1/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39591—Stabilisation, fragmentation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype

Landscapes

  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
EP10797631.8A 2009-07-08 2010-06-29 Design of stable and aggregation free antibody fc molecules through ch3 domain interface engineering Active EP2451840B1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US22383109P 2009-07-08 2009-07-08
PCT/US2010/040471 WO2011005621A1 (en) 2009-07-08 2010-06-29 Design of stable and aggregation free antibody fc molecules through ch3 domain interface engineering

Publications (3)

Publication Number Publication Date
EP2451840A1 EP2451840A1 (en) 2012-05-16
EP2451840A4 true EP2451840A4 (en) 2014-01-22
EP2451840B1 EP2451840B1 (en) 2018-12-26

Family

ID=43429484

Family Applications (1)

Application Number Title Priority Date Filing Date
EP10797631.8A Active EP2451840B1 (en) 2009-07-08 2010-06-29 Design of stable and aggregation free antibody fc molecules through ch3 domain interface engineering

Country Status (7)

Country Link
US (1) US9308258B2 (en)
EP (1) EP2451840B1 (en)
JP (1) JP2012532608A (en)
AU (1) AU2010270844A1 (en)
CA (1) CA2766166A1 (en)
MX (1) MX2011013455A (en)
WO (1) WO2011005621A1 (en)

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US9493578B2 (en) 2009-09-02 2016-11-15 Xencor, Inc. Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens
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US8637641B2 (en) 2010-07-29 2014-01-28 Xencor, Inc. Antibodies with modified isoelectric points
US8551479B2 (en) 2010-09-10 2013-10-08 Oncomed Pharmaceuticals, Inc. Methods for treating melanoma
EP2635607B1 (en) 2010-11-05 2019-09-04 Zymeworks Inc. Stable heterodimeric antibody design with mutations in the fc domain
PL3485903T3 (en) 2011-09-23 2023-06-12 Mereo Biopharma 5, Inc. Vegf/dll4 binding agents and uses thereof
US10851178B2 (en) 2011-10-10 2020-12-01 Xencor, Inc. Heterodimeric human IgG1 polypeptides with isoelectric point modifications
JP6326371B2 (en) 2011-11-04 2018-05-16 ザイムワークス，インコーポレイテッド Stable heterodimeric antibody design with mutations in the Fc domain
EP2830646B1 (en) 2012-03-27 2018-03-07 NGM Biopharmaceuticals, Inc. Compositions and methods of use for treating metabolic disorders
WO2014004586A1 (en) 2012-06-25 2014-01-03 Zymeworks Inc. Process and methods for efficient manufacturing of highly pure asymmetric antibodies in mammalian cells
JP6371294B2 (en) 2012-10-31 2018-08-08 オンコメッド ファーマシューティカルズ インコーポレイテッド Methods and monitoring of treatment with DLL4 antagonists
JP6026002B2 (en) * 2012-11-27 2016-11-16 アルテオジェン インコーポレイテッド Composition for stabilizing a fusion protein in which a protein and an Fc domain are fused
TW201425336A (en) 2012-12-07 2014-07-01 Amgen Inc BCMA antigen binding proteins
CA2892756C (en) 2012-12-07 2020-04-14 Pfizer Inc. Engineered monomeric antibody fragments
US9701759B2 (en) 2013-01-14 2017-07-11 Xencor, Inc. Heterodimeric proteins
US10487155B2 (en) 2013-01-14 2019-11-26 Xencor, Inc. Heterodimeric proteins
AU2014205086B2 (en) 2013-01-14 2019-04-18 Xencor, Inc. Novel heterodimeric proteins
US10131710B2 (en) 2013-01-14 2018-11-20 Xencor, Inc. Optimized antibody variable regions
US11053316B2 (en) 2013-01-14 2021-07-06 Xencor, Inc. Optimized antibody variable regions
US10968276B2 (en) 2013-03-12 2021-04-06 Xencor, Inc. Optimized anti-CD3 variable regions
US9605084B2 (en) 2013-03-15 2017-03-28 Xencor, Inc. Heterodimeric proteins
AU2014207549B2 (en) 2013-01-15 2018-12-06 Xencor, Inc. Rapid clearance of antigen complexes using novel antibodies
WO2014120619A2 (en) 2013-01-30 2014-08-07 Ngm Biopharmaceuticals, Inc. Compositions and methods of use in treating metabolic disorders
US9161966B2 (en) 2013-01-30 2015-10-20 Ngm Biopharmaceuticals, Inc. GDF15 mutein polypeptides
US10519242B2 (en) 2013-03-15 2019-12-31 Xencor, Inc. Targeting regulatory T cells with heterodimeric proteins
US10106624B2 (en) 2013-03-15 2018-10-23 Xencor, Inc. Heterodimeric proteins
US10858417B2 (en) 2013-03-15 2020-12-08 Xencor, Inc. Heterodimeric proteins
US10544187B2 (en) 2013-03-15 2020-01-28 Xencor, Inc. Targeting regulatory T cells with heterodimeric proteins
CA2931356A1 (en) 2013-11-27 2015-06-04 Zymeworks Inc. Bispecific antigen-binding constructs targeting her2
AP2016009475A0 (en) 2014-03-28 2016-09-30 Xencor Inc Bispecific antibodies that bind to cd38 and cd3
CN106573966B (en) 2014-07-30 2022-03-01 Ngm生物制药有限公司 Compositions and methods for treating metabolic abnormalities
US9821059B2 (en) 2014-10-17 2017-11-21 Alteogen Inc. Composition for stabilizing protein and pharmaceutical formulation comprising the same
CN107530419B (en) 2014-10-31 2021-05-18 昂考梅德药品有限公司 Combination therapy for treating disease
MD20170035A2 (en) 2014-10-31 2017-09-30 Ngm Biopharmaceuticals Inc Compositions and methods of use for treating matabolic disorders
US10259887B2 (en) 2014-11-26 2019-04-16 Xencor, Inc. Heterodimeric antibodies that bind CD3 and tumor antigens
MX2017006918A (en) 2014-11-26 2018-01-25 Xencor Inc Heterodimeric antibodies that bind cd3 and cd38.
PE20171324A1 (en) 2014-11-26 2017-09-11 Xencor Inc HETERODIMERIC ANTIBODIES THAT BIND CD3 AND TUMOR ANTIGENS
WO2016105450A2 (en) 2014-12-22 2016-06-30 Xencor, Inc. Trispecific antibodies
WO2016141387A1 (en) 2015-03-05 2016-09-09 Xencor, Inc. Modulation of t cells with bispecific antibodies and fc fusions
IL244857B (en) * 2015-04-02 2020-11-30 The Israel Inst Of Biological Resesrch Iibr Acetylcholinesterase-fc domain fusion protein
EP3307321A4 (en) 2015-08-26 2019-04-17 Bison Therapeutics Inc. Multispecific antibody platform and related methods
ES2968074T3 (en) 2015-09-23 2024-05-07 Mereo Biopharma 5 Inc Bi-specific anti-VEGF/DLL4 antibody for use in the treatment of platinum-resistant ovarian cancer
EP3387013B1 (en) 2015-12-07 2022-06-08 Xencor, Inc. Heterodimeric antibodies that bind cd3 and psma
TWI815793B (en) 2016-03-31 2023-09-21 美商恩格姆生物製藥公司 Binding proteins and methods of use thereof
RU2767357C2 (en) 2016-06-14 2022-03-17 Ксенкор, Инк. Bispecific checkpoint inhibitors antibodies
CA3029328A1 (en) 2016-06-28 2018-01-04 Xencor, Inc. Heterodimeric antibodies that bind somatostatin receptor 2
US10793632B2 (en) 2016-08-30 2020-10-06 Xencor, Inc. Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors
WO2018071919A1 (en) 2016-10-14 2018-04-19 Xencor, Inc. IL15/IL15Rα HETERODIMERIC FC-FUSION PROTEINS
CA3065171A1 (en) 2017-06-05 2018-12-13 Janssen Biotech, Inc. Engineered multispecific antibodies and other multimeric proteins with asymmetrical ch2-ch3 region mutations
CN111132733A (en) 2017-06-30 2020-05-08 Xencor股份有限公司 Targeted heterodimeric Fc fusion proteins containing IL-15/IL-15R α and an antigen binding domain
CN112272563A (en) 2017-11-08 2021-01-26 Xencor股份有限公司 Bispecific and monospecific antibodies using novel anti-PD-1 sequences
US10981992B2 (en) 2017-11-08 2021-04-20 Xencor, Inc. Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors
KR20200100098A (en) 2017-12-19 2020-08-25 젠코어 인코포레이티드 Engineered IL-2 FC fusion protein
WO2019195623A2 (en) 2018-04-04 2019-10-10 Xencor, Inc. Heterodimeric antibodies that bind fibroblast activation protein
JP2021521784A (en) 2018-04-18 2021-08-30 ゼンコア インコーポレイテッド PD-1 targeted heterodimer fusion proteins containing IL-15 / IL-15RaFc fusion proteins and PD-1 antigen binding domains and their use
KR20210003814A (en) 2018-04-18 2021-01-12 젠코어 인코포레이티드 TIM-3 targeting heterodimer fusion protein containing IL-15/IL-15Rα Fc-fusion protein and TIM-3 antigen binding domain
WO2020072821A2 (en) 2018-10-03 2020-04-09 Xencor, Inc. Il-12 heterodimeric fc-fusion proteins
AU2019359475A1 (en) 2018-10-12 2021-05-20 Xencor, Inc. PD-1 targeted IL-15/IL-15Ralpha Fc fusion proteins and uses in combination therapies thereof
US11618776B2 (en) 2018-12-20 2023-04-04 Xencor, Inc. Targeted heterodimeric Fc fusion proteins containing IL-15/IL-15RA and NKG2D antigen binding domains
MX2021010390A (en) 2019-03-01 2021-11-17 Xencor Inc Heterodimeric antibodies that bind enpp3 and cd3.
TW202128757A (en) 2019-10-11 2021-08-01 美商建南德克公司 Pd-1 targeted il-15/il-15ralpha fc fusion proteins with improved properties
US11919956B2 (en) 2020-05-14 2024-03-05 Xencor, Inc. Heterodimeric antibodies that bind prostate specific membrane antigen (PSMA) and CD3
WO2022040482A1 (en) 2020-08-19 2022-02-24 Xencor, Inc. Anti-cd28 and/or anti-b7h3 compositions
IL305736A (en) 2021-03-09 2023-11-01 Xencor Inc Heterodimeric antibodies that bind cd3 and cldn6
EP4305065A1 (en) 2021-03-10 2024-01-17 Xencor, Inc. Heterodimeric antibodies that bind cd3 and gpc3

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WO2007124077A2 (en) * 2006-04-21 2007-11-01 Amgen, Inc. Immunoglobulin constant region domains with enhanced stability

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PL2235064T3 (en) 2008-01-07 2016-06-30 Amgen Inc Method for making antibody fc-heterodimeric molecules using electrostatic steering effects
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CN102558355B (en) * 2011-12-31 2015-02-25 苏州康宁杰瑞生物科技有限公司 Heterodimeric FC (fragment crystallizable) modification method based on charge network and preparation method of heterodimeric proteins

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WO2007022070A2 (en) * 2005-08-12 2007-02-22 Amgen Inc. Modified fc molecules
WO2007124077A2 (en) * 2006-04-21 2007-11-01 Amgen, Inc. Immunoglobulin constant region domains with enhanced stability

Non-Patent Citations (2)

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Title
DALL'ACQUA WILLIAM ET AL: "Contribution of domain interface residues to the stability of antibody CH3 domain homodimers", BIOCHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 37, no. 26, 30 June 1998 (1998-06-30), pages 9266 - 9273, XP002245748, ISSN: 0006-2960, DOI: 10.1021/BI980270I *
See also references of WO2011005621A1 *

Also Published As

Publication number Publication date
EP2451840B1 (en) 2018-12-26
AU2010270844A1 (en) 2011-12-22
MX2011013455A (en) 2012-02-13
JP2012532608A (en) 2012-12-20
EP2451840A1 (en) 2012-05-16
US9308258B2 (en) 2016-04-12
US20120116057A1 (en) 2012-05-10
CA2766166A1 (en) 2011-01-13
WO2011005621A1 (en) 2011-01-13

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